Potassium Carbonate → 6-tert-butyl-2-{3-[5-(1'-ethyl-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-6-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-one

HRID 1431117노트

반응식

HRID 1431117 반응식
C([O:4][CH2:5][C:6]1[C:11]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([CH:25]4[CH2:30][CH2:29][N:28]([CH2:31][CH3:32])[CH2:27][CH2:26]4)=[CH:21][N:20]=3)[C:15](=[O:33])[N:14]([CH3:34])[N:13]=2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:35]1[N:44]=[CH:43][C:42]2[C:37](=[C:38]([F:49])[CH:39]=[C:40]([C:45]([CH3:48])([CH3:47])[CH3:46])[CH:41]=2)[C:36]1=[O:50])(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO>[C:45]([C:40]1[CH:41]=[C:42]2[C:37](=[C:38]([F:49])[CH:39]=1)[C:36](=[O:50])[N:35]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[N:20]=[CH:21][C:22]([CH:25]5[CH2:30][CH2:29][N:28]([CH2:31][CH3:32])[CH2:27][CH2:26]5)=[CH:23][CH:24]=4)[C:15](=[O:33])[N:14]([CH3:34])[N:13]=3)[C:6]=1[CH2:5][OH:4])[N:44]=[CH:43]2)([CH3:46])([CH3:47])[CH3:48]

참가 물질

4

반응물 2

HCID 11430Potassium CarbonateHCID 667432512-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(1-ethylpiperidin-4-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

생성물 1

HCID 566558096-tert-butyl-2-{3-[5-(1'-ethyl-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-6-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-one수율 78.4%

시약·촉매·용매 1

HCID 887Methanol용매

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온도
40 °C

실험 절차

To 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(1-ethylpiperidin-4-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate (147 mg, 216 μmol, Eq: 1.00) in MeOH (15 ml) was added potassium carbonate (59.8 mg, 432 μmol, Eq: 2.0). The reaction mixture stirred at 40° C. for 1 h. The solution was cooled to room temperature. Concentrated in vacuo. The residue was taken up in DCM/water and the layers were separated. The aqueous layer was extracted once with DCM. The organic layers were combined, and then dried over Na2SO4. Concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 12 g, 25% to 75% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient) to give 6-tert-butyl-2-{3-[5-(1′-ethyl-1′,2′,3′,4′,5′,6′-hexahydro-[3,4′]bipyridinyl-6-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-one (108 mg, 78%). LC/MS-ESI observed [M+H]+ 638. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.16 (br. s., 2H) 1.43 (s, 9H) 1.84 (br. s., 4H) 2.06 (br. s., 2H) 2.51 (br. s., 3H) 3.11 (br. s., 2H) 3.69-4.09 (m and overlapping singlet, 4H) 4.42 (d, J=6.80 Hz, 2H) 6.91 (d, J=8.69 Hz, 1H) 7.37-7.77 (m, 6H) 8.11-8.36 (m, 3H) 8.60 (s, 1H)

후처리

  1. temperatureThe solution was cooled to room temperature
  2. concentrationConcentrated in vacuo
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted once with DCM
  5. dry with materialdried over Na2SO4
  6. concentrationConcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 12 g, 25% to 75% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient)

출처 및 근거

ORD 기록
ord-350c7722f9cb4966990afe3e52475204
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940741B2

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